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骨髓衍生的肌成纤维细胞通过 IL-6/JAK2/STAT3 通路促进结肠肿瘤的发生。

Bone marrow-derived myofibroblasts promote colon tumorigenesis through the IL-6/JAK2/STAT3 pathway.

机构信息

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

出版信息

Cancer Lett. 2014 Feb 1;343(1):80-9. doi: 10.1016/j.canlet.2013.09.017. Epub 2013 Oct 18.

DOI:10.1016/j.canlet.2013.09.017
PMID:24145153
Abstract

Bone marrow-derived myofibroblasts (BMFs) have been shown to promote tumor growth. Here, we found that BMFs or BMF conditioned medium (BMF-CM) induced cancer stem cell-like sphere formation of colon cancer cells. The co-cultured BMFs, but not co-cultured cancer cells, expressed higher levels of IL-6 than BMFs or cancer cells cultured alone. Anti-mouse IL-6 neutralizing antibody, JAK2 inhibitors and STAT3 knockdown in mouse cancer cells reduced BMF- and BMF-CM-induced sphere formation of colon cancer cells. When co-injected, BMFs significantly enhanced tumorigenesis of colon cancer cells in mice. Our results demonstrate that BMFs promote tumorigenesis via the activation of the IL-6/JAK2/STAT3 pathway.

摘要

骨髓来源的肌成纤维细胞(BMFs)已被证明可促进肿瘤生长。在这里,我们发现 BMFs 或 BMF 条件培养基(BMF-CM)可诱导结肠癌细胞形成类似癌症干细胞的球体。共培养的 BMFs 表达的 IL-6 水平高于单独培养的 BMFs 或癌细胞,而共培养的癌细胞则没有。抗小鼠 IL-6 中和抗体、JAK2 抑制剂和 STAT3 敲低可降低小鼠癌症细胞中 BMF 和 BMF-CM 诱导的结肠癌细胞球体形成。当共注射时,BMFs 可显著增强小鼠结肠癌细胞的致瘤性。我们的结果表明,BMFs 通过激活 IL-6/JAK2/STAT3 通路促进肿瘤发生。

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